The invention relates to a concentration method for the concentration of material in a liquid, to a concentration device for the carrying out of the method and to a reaction method using the concentration method.
Especially in biological research or diagnostics, the problem frequently arises of having material particles, in particular cells or co-called beads, react with one another or with biological macromolecules such as nucleic acids, proteins, antigens, antibodies, etc. Beads designate microspheres of a diameter of some 100 nm up to some μm onto which a reaction starting material is coated. An example for these are latex agglutination assays such as are described in U.S. Pat. No. 4,960,715. There, latex spheres are used as beads having a diameter of some 100 nm up to some μm and are coated either with antigens or antibodies. Either antibodies or antigens are then accordingly detected in the liquid sample which react with the molecules on the beads and which can link the beads to one another. This so-called agglutination or aggregation can be evaluated optically and serves for the detection of the presence of the antibodies or antigens in the sample. In the present text, the term “reaction” should, where applicable, also include the linking process between the beads.
The material particles in the liquid which should react with one another come together based on diffusion. This process can be reinforced by active mixing or agitating.
It would be desirable for the individual material particles to be brought close to one another in the solution to increase the reaction probability. This can e.g. be achieved by a sufficiently high concentration of particles in the solution. Frequently, however, sufficient material is not available to achieve a desirably high concentration. This problem is in particular also encountered when cell-cell interacts in a solution, the reaction of cells with coated beads or of differently coated beads with one another should be examined.
It is also desirable in some applications to achieve a concentration of material particles in a solution independently of a reaction in which the reaction starting materials should be brought close to one another.
A known method for concentration is the use of filters, membranes or other porous media such as is described in U.S. Pat. No. 6,887,384. However, with a filter, non-specific reactions with the filter wall can occur and as a rule transmission measurements at the concentrated medium are impossible.
Another possibility for concentration is centrifugation such as used in the enrichment of uranium. For this purpose, a reaction vessel must be introduced into a centrifuge and be removed from it again after the centrifugation to be able to carry out a measurement so that the method is complex and/or expensive.